The progress during the past four years and future plans are: 1) Longitudinal: This component has focused on a 25-year follow-up of the then large-scale epidemiologic study ("Vietnam Drug User Returns") conducted in the early 1970's. The main follow-up data collection has been completed after decades of hiatus, with continued fundings starting to complete database archiving, data analyses, and dissemination ("Washington University Vietnam Era Study Phase III (VES-III)," R01DA09379, R01DA09281). The future plans are to: 1a) complete data analyses and main publications from VES-III; 1b) conduct a followback investigation on the decreased extent of bias inherent in such censored data; 1c) plan and conduct small-scale studies related to intervention for selected high-risk subgroups of the VES-III cohort; and 1d) begin preparation for an offspring study of the VES-III cohort. 2) Cross-Cultural/International: This component centers on the notion of cross-culturally unique protective factors and their moderating effects. The first phase which aims at replicating a developmental psycho pathology model substantiated in the western literature, using an existing large database from five countries ("Cross-Cultural Epidemiology-Phase I (CC-I)," R01DK10021), is currently in the second year of funding. Future plans are to: 2a) complete data analyses and main publications for CC-I; 2b) plan and begin implementing a study to examine adolescent substance use and mental health among the Japanese and Vietnamese, focusing on protective factors and their decay process, using an embedded cohort-sequential, migration design ("Pacific Rim" Project); 2c) implement a feasibility study to conduct substance abuse and psychiatric interviews and collect DNA from Japanese adolescents to study gene-environment interaction effects rising from the presence of ethnic-specific alcohol sensitivity genes and their consequences to other drug use ("Flushing Syndrome," P50AA11998, Pilot 3); 2d) explore potentials for collecting DNA from the Pacific Rim Study cohorts to incorporate genetic immunity to use of alcohol and potentially other psychoactive substances to the understanding of environmental moderators; 2e) explore potentials for future comparative analyses of the data on the Vietnamese adolescent against trauma and its relation to substance abuse ("Crossroad" Study). In the next five years, the P.I. plans to: reach closure to VES-III (1a), the followback extension (1b), CC-I (2a), and the Flushing Syndrome feasibility (2c); implement VES-III intervention (1c) and the Pacific Rim Project (2b); begins preparatory work for the remaining (1d, 2d, 2e). 3) Methodological Enhancement component continues previous attempts to integrate novel technologies to more traditional statistical methods to improve epidemiologic prediction and explanatory precision.